EP2995605B1

EP2995605B1 - Method for preparing a reduced coenzyme q10 powder.

Info

Publication number: EP2995605B1
Application number: EP14788075.1A
Authority: EP
Inventors: Xinde Xu; Gang Chen; Xuejun Lao; Lihua Zhang; Xiaoxia Sun; Xiaoyue Jiang
Original assignee: Zhejiang Medicine Co Ltd Xinchang Pharmaceutical Factory
Current assignee: Zhejiang Medicine Co Ltd Xinchang Pharmaceutical Factory
Priority date: 2013-04-25
Filing date: 2014-03-14
Publication date: 2022-11-16
Anticipated expiration: 2034-03-14
Also published as: CN104119209A; CN104119209B; EP2995605A1; EP2995605A4; JP2016520037A; WO2014173174A1; US10028914B2; US20160101053A1

Description

FIELD OF THE INVENTION

The present invention relates to a method for preparing a reduced coenzyme Q10 powder.

BACKGROUND OF THE INVENTION

Coenzyme Q10 is a fat-soluble compound widely existed in organisms and is widely distributed in nature, mainly in yeast, plant leaves, seeds and cells of heart, liver and kidney of animals. Coenzyme Q10 is one of the most important coenzyme in human body. The main function of coenzyme Q10 is to scavenge free radicals, anti-tumor, enhance immunity, promote metabolism and improve hypoxia tolerance of heart, etc.
The existing states of coenzyme Q10 are usually in two kinds of oxidized coenzyme Q10 and reduced coenzyme Q10. Reduced coenzyme Q10 is referred to as Ubiquinol with a white crystal. Oxidized coenzyme Q10 is referred to as Ubiquinone with a yellow crystal . Their structural formulas are as follows:
Reduced coenzyme Q10 is an important cell metabolism activator to breathe and immunopotentiator, and has effects of inoxidizability, scavenging free radicals, beauty skin care, reducing blood sugar, decompression, preventing vascular atherosclerosis, improving chronic respiratory disease and so on. In comparison with oxidized coenzyme Q10, reduced coenzyme Q10 has higher absorptivity and higher bioavailability. Reduced coenzyme Q10 has been widely used in the field of pharmaceuticals, health foods, foods, cosmetics and so on.
Sources of reduced coenzyme Q10 in the art can basically be divided into three categories such as chemical synthesis, microbial fermentation, animals extracts and plants extracts. In industry, oxidized coenzyme Q10 is always obtained by reduction reaction in the presence of reductant and crystallization in an organic solvent such as alcohol after the reduction reaction. US2004019788A1 describes a method for crystallization of reduced coenzyme Q10 in aqueous solution such as organic solvent replaced by water or mixture of water and organic solvent. US, 2008/026063 A1 discloses a composition wherein an oil component containing reduced coenzyme Q10 is polydispersed forming a domain in a matrix containing a water-soluble excipient and a production method thereof. According to one specific example of the production method, the oil in water composition is spray dried with hot air using a spray drier. US 20050074860 A1 also describes a method of dissolving reduced coenzyme Q10 crystal in oil and recrystallization after cooling to obtain a new crystal. It was reported that crystal was changed and its bioavailability was improved. It can be seen from the X-ray diffraction spectrum that two of crystals are in small proportion and in less bioavailability. Moreover, it is difficult to remove vegetable oil on the surface of crystals obtained by this method; or it needs a lot of toxic solvents such as n-hexane washing to remove the vegetable oil on the surface of crystals. These limit extensive application of the crystals. Therefore, it is necessary to find a way to obtain reduced coenzyme Q10 powder and composition comprising the reduced coenzyme Q10 powder with smaller crystallinity, higher bioavailability and convenient application.

SUMMARY OF THE INVENTION

According to the present invention, it is provided a method for preparing a reduced coenzyme Q10 powder according to claim 1.
The method according to the invention comprises the steps as follows:

(1) adding an oxidized coenzyme Q10 into an organic solvent, heating to 50°C∼ 60°C of temperature, and adding a reductant for reaction; wherein the reductant is selected from one or more of hyposulphurous acid or salt thereof, ascorbic acid or salt thereof, carbodithioic acid or salt thereof, or reductase; the organic solvent is ketones, or hydrophobic alkanes; and
(2) removing the organic solvent after finishing the reaction to obtain a molten and oily reduced coenzyme Q10 liquid; and then heating the molten and oily reduced coenzyme Q10 liquid to 50°Cof temperature, spraying by a centrifugal sprayer, to form particles in cold air after spraying, to obtain a white reduced coenzyme Q10 powder.

Preferably, the hyposuphurous acid or salt thereof is thiosulfuric acid or sodium thiosulfate; the ascorbic acid or salt thereof is ascorbic acid or sodium ascorbate; the dithiosulfuric acid or salt thereof is dithiosulfuric acid or sodium dithiosulfate; the reductase is phosphorylation biological reductase; the ketone is acetone; the hydrophobic paraffin is n-hexane.
Preferably, the temperature of the cold air is not higher than 30°C; more Preferably, the temperature of the cold air is not higher than 10°C.
Preferably, the cold air is conventional air, air without oxygen or nitrogen.
Preferably, spraying is performed by using centrifugal sprayer or pressure sprayer when spraying.
The method of the present invention further comprises adding antioxidant, stabilizer, absorption enhancer and/or excipient as adjuvants to the reduced coenzyme Q10 liquid before spraying, to obtain the reduced coenzyme Q10 powder with adjuvants; or re-melting the reduced coenzyme Q10 powder or the reduced coenzyme Q10 powder with the adjuvants, and then mixing it with antioxidant, stabilizer, absorption enhancer and/or excipient as adjuvants, to obtain the reduced coenzyme Q10 powder by a spraying drying method.
Preferably, the antioxidant is selected from one or more of vitamin E, butyl hydroxy toluene, ascorbic acid and vitamin A. The stabilizer is selected from one or more of gelatin, casein, sodium caseinate, soybean protein, modified starch, cyclodextrin and gum Arabic. The absorption enhancer is selected from one or more of polyglycerol fatty acid ester, glycerin, stearic acid, oleic acid and linoleic acid. The excipient is sugar and/or dextrin.
Preferably, antioxidants and/or stabilizers, and/or excipients, and/or absorption enhancer is added to the reduced coenzyme Q10 liquid, and then spraying in a sprayer, drying and styling the sprayed drops at 190°C of temperature in hot air after spraying, to obtain the reduced coenzyme Q10 powder.
Preferably, the dosage form of the reduced coenzyme Q10 powder is tablets or capsules, for dietary supplement.
In particular, by the aforementioned method in accordance with claim 1 a dry power with lower crystals is obtained.
Moreover, in comparison with the crystals obtained by solvents or vegetable oil crystallization, the reduced coenzyme Q10 powder obtained by the method in accordance with claim 1 shows in Cu-Ka ray X diffraction spectrum different characteristics of crystals and also shows different melting points by Differential Scanning Thermal analyzer(DSC). More specifically, in an intermediate step of the method in accordance with claim 1, an oily reduced coenzyme Q10 liquid is obtained.
The reductant in the reaction is selected from one or more of disulfurous acid or salts thereof, ascorbic acid or salt thereof, dithiosulfuric acid or salt thereof, enzymes, and so on.
The organic solvent in reaction are ketones orhydrophobic alkanes. It does also not add organic solvents due to the melting point of coenzyme Q10 nearly 50°C, it may directly heat the reacted liquid up to nearly 60°C, the reactants react with a reductant in the molten state.
If a hydrophobic organic solvent is used in the reaction, a plenty of water is added for layering after finishing the reaction, to remove redundant reductant and water soluble impurities, to volatilize organic solvents of the organic layer in vacuum to obtain an oily reduced coenzyme Q10.
The oily reduced coenzyme Q10 may be sprayed in a spraying drying tower. The difference from conventional blowing hot air in a spraying drying tower is that a cold air is blown into a spraying drying tower, due to the melting point of the reduced coenzyme Q10 nearly 50 °C , the reduced coenzyme Q10 droplets immediately condenses into a white solid powder when blowing the cold air.
After melting the reduced coenzyme Q10 crystal, centrifugal spraying is performed. The viscosity of the liquid before sprying may be 450 CPA, the rotational speed of atomizing disk may be 15000rpm, the particle diameter of the product may be 180µm. The parameters can be properly adjusted, according to different particle sizes of products and different methods of production.
During the process, the temperature of the cold air is not higher than 30°C, preferably is not higher than 10°C. The lower the temperature is, the more conducive to the cold cure of reduced coenzyme Q10 droplet. In order to prevent the oxidation of the reduced coenzyme Q10, preferably the blowing cold air is the air, the air without oxygen or nitrogen.
Moreover, in order to increase the stability or enhance the bioavailability of the reduced coenzyme Q10 dry powder, the coenzyme Q10 liquid in molten state can be added by suitable antioxidants such as vitamin E, butylated hydroxytoluene, ascorbic acid, vitamin A and so on, also can be added by absorption enhancers such as surfactant, glyceric acid, fatty acid, etc., according to needs.
Furthermore, in order to enhance the stability of the reduced coenzyme Q10 powder, the molten reduced coenzyme Q10 can be mixed with adjuvants before spraying, the adjuvants may be colloid such as gelatin, casein, sodium caseinate, soybean protein, starchy such as modified starch, cyclodextrin, polysaccharide such as gum Arabic; or a certain amount of excipients such as sugar, dextrin; or emulsifier, stabilizer, and then blow in hot air after mixing, and then to obtain the reduced coenzyme Q10 powder after spraying and drying.
By the method of the present invention, the reduced coenzyme Q10 obtained by the method of the present invention has a higher purity over 98%. The melting point thereof is lower than that of conventional solvent crystallization method, due to a stable crystallization has a higher melting point. A substable crystallization has a lower melting point. It is illustrated from these results that the crystallization degree of the reduced coenzyme Q10 declines, the amorphous degree thereof increases.
In comparison with the crystals crystallized by conventional solvent method, it may be shown from X diffraction spectrum that the reduced coenzyme Q10 powder of the present invention obtained by spraying condensation has a very strong absorption peak at the diffraction angle 2θ=22.8°in the X-ray diffraction spectrum, the intensity of a absorption peak is decreased obviously at other diffraction angle. Especially relative to the peak 18.9°, both of the intensity of peak 27.4° and peak 30.3° are less than 0.1; the intensity of peak 22.8° is 100, the intensity of peak 20.0° strength is less than 40.0, the intensity of peak 18.9 °is less than 90.0.
For the crystals obtained by conventional solvent crystallization method, a strong absorption peaks appear at 3.0° , 4.6°, 20.1°, 22.8°, 27.4° and 30.3°. In particular, a strong absorption peak appears at 18.7 ° and 18.9 °. And relative to peak 18.9°, the intensity of peak 27.4° and 30.3° is more than 0.1; the intensity of peak 22.8 °is 100, the intensity of peak 20.0° strength is less than 40.0, the intensity of peak 18.9 ° is less than 200.0.
After the comparison, a strong peak at 18.7° in X-ray diffraction spectrum of the reduced coenzyme Q10 powder of the present invention is disappeared, the intensity of other place peaks such as 3.0°, 4.6°, 18.9°, 20.1°, 22.8°, 27.4°, 30.3° 3.0 ° and 4.6 °, 18.9 ° and 20.1 ° and 22.8 ° and 27.4 ° and 30.3 °decreased significantly. The height of diffraction peak represents a size of the crystallinity. Therefore, the crystallinity of the reduced coenzyme Q10 powder of the present invention is decreased.
In addition, a white reduced coenzyme Q10 powder is used for a series of crystal characteristics analysis and biological utilization experiment in animals. The crystallinity reduction of pharmaceutical powder can increase the bioavailability of pharmaceuticals.
The reduced coenzyme Q10 powder with a reduced crystallinity obtained by the present invention, not only improves the stability, but also shows higher bioavailability in organisms. The reduced coenzyme Q10 powder can be used for foods, nutritions, health care products, cosmetics, pharmaceuticals and so on, and the application forms can be directly in the form of powder, tablet, capsule, or other appropriate composition by adding others such as excipients, colorants, antioxidants, diluent, absorption accelerants. The reduced coenzyme Q10 powder of the present invention is in incomplete crystallization and has good stability and excellent oral bioavailability, suitable for application in health food, cosmetics, medicines, etc. The reduced coenzyme Q10 powder resulting from the method according to the present invention shows a strong peak at the diffraction angle 2θ=18.9° and a strong absorption peak at 22.8° in Cu - Kα ray X-diffraction spectrum, and also meet one or more of the following (a) ∼ (d) items:

(a) the peak intensity at 22.8° is 100, the peak intensity at 20.0°is less than 40.0;
(b) the peak intensity at 22.8° is 100, the peak at 18.9° is less than 90.0;
(c)the intensity ratio of peak 27.4° to peak 18.9° is less than 0.1;
(d)the intensity ratio of peak 30.3° to peak 18.9° is less than 0.1.

Preferably, a melting point of the reduced coenzyme Q10 powder prepared by the method according to the present invention is determined by DSC is 46.9 °C. It is obviously lower than a melting temperature (49.5 °C) of crystals obtained by conventional solvent crystallization.

BRIEF DESCRIPTION OF FIGURES

Figure 1 is an X-ray diffraction spectrum of the reduced coenzyme Q10 powder obtained by spraying oily reduced coenzyme Q10 in blowing cold air;
Figure 2 is an X-ray diffraction spectrum of the reduced coenzyme Q10 powder obtained by crystallization in ethanol solvent of conventional methods;
Figure 3 is a DSC spectrum of the reduced coenzyme Q10 powder obtained by spraying oily reduced coenzyme Q10 in blowing cold air;
Figure 4 is a DSC spectrum of the reduced coenzyme Q10 powder obtained by crystallization in ethanol solvent of conventional methods.

DETAILED DESCRIPTION AND PREFERRED EMBODIMENTS THEREOF

Hereafter, the present invention will be described specifically with reference to the examples. The examples are given only for illustration of the technical solution of the present invention and should not be construed to limit the present invention.

EXAMPLE 1

100g oxidized coenzyme Q10 is added to 1000 mL n-hexane, heated to 50°C of temperature after mixing. 1000 mL 20% (w/w) sodium thiosulfate solution is added to the reaction solution and stirred at 50°C for 1 hour, and then layered to a water layer as a lower layer and a n-hexane layer after finishing the reaction, the n-hexane layer is washed by 25% (w/w) salt water, and then recycle n-hexane at 35°C in vacuum, to form a paste and then heat the paste to 50°C of temperature, spray by centrifugal sprayer, and form pellet at 10°C in cold air after spraying, to obtain white reduced coenzyme Q10 powder 96.8 g (Sample1) with the purity is 99.5% and the average powder particle size is 154 mm.

Experiment for determining a proportion of the reduced coenzyme Q10 in the reduced coenzyme Q10 powder or crystals by the HPLC method

Determining the proportion of reduced coenzyme Q10 in reduced coenzyme Q10 powder or crystals by the HPLC method. Determination conditions are as follows:

Instruments: Agilient 1210
Column: C18 column
Mobile phase: ethanol/ methanol= 4/3(V/V)
Detection wavelength: 210 nm
Flow velocity: 1ml/min

The weight ratio of reduced coenzyme Q10 to oxidized coenzyme Q10 in Sample 1 by determination of the HPLC method is 99.2/0.8.
It can be seen from it that the reduced coenzyme Q10 has a higher purity than 98% in the reduced coenzyme Q10 powder of the present invention.

Experiment for determining diffraction peaks of the reduced coenzyme Q10 powder or crystal by X-ray diffraction

Determine the diffraction peak of the reduced coenzyme Q10 powder or crystal by X-ray diffraction method. It can determine from the X-ray diffraction spectrum of diffraction peak position and intensity that the crystal shape changes. Determination of the present invention is made by a Cu-Ka ray X diffraction device. Determination conditions are as follows:

Instrument models: X-ray powder diffraction Bruker D8 Advance
Ray intensity: 40kV, 100mA
Angle range: 2θ=2∼60°
Scanning speed: 2°/min
Scanning step: 0.05°
Divergence slit: 1°
Accept the slit: 0.60°
Scattering slit: 1°

X-ray diffraction spectrum of Samples 1 determined by the Cu-Ka ray X diffraction method is shown in Figure 1. The diffraction angle 2θ in the diffraction spectrum has a strong peak at 18.9°, and has a very strong absorption peak at 22.8 °, and another diffraction angle peak intensity is decreased obviously, especially, a strength of peak 27.4° and 30.3°relative to peak 18.9° is less than 0.1. A peak strength at 22.8°is as 100. A peak strength at 20.0° is less than 40.0. A peak strength at 18.9° is less than 90.0.

Experiment for determining the melting point of the reduced coenzyme Q10 powder or crystal by thermogravimetric analyzer

Determine the melting point of the reduced coenzyme Q10 powder or crystal by thermogravimetric analyzer. Degree of amorphous and crystallization of reduced coenzyme Q10 can be determined by the melting point. Determination conditions of the present invention are as follows:

Instrument: Universal V4.7A TA Instruments
Temperature scope: 30-100°C
Heating rate: 2.5°C/min
Sample amount: 15mg

Samples 1 is scanned for melting point by differential scanning thermal analyzer, its differential scanning map is shown in Figure 3. It can be seen from it that the melting point is 46.9 °C.
It can be seen from it that the crystal melting point of the present invention is lower than that of conventional solvent crystallization method, because the melting point of stable crystallization is higher, and the melting point of metastable crystallization is lower. The result illustrates that the crystallization degree of reduced coenzyme Q10 declines, its amorphous degree increases.

EXAMPLE 2 (Comparative example: crystallization)

100g oxidized coenzyme Q10 is added into 1000 mL n-hexane, heated to a 50°C of temperature after mixing. 1000 mL 20% (w/w) sodium hydrosulfite solution is added to the reaction solution, and stirred at 50°C for 1 hour and then. layered to a water layer as a lower layer and a n-hexane layer after finishing the reaction, the n-hexane layer is washed by 25% (w/w) salt water, and then recycle n-hexane at 35°C in vacuum, to form a paste and then add 1100 ml of anhydrous ethanol and heated to 50°C to be dissolved, then add 350 ml water to the solution under stirring, and cool to 5°C to crystallization., to obtain 95.2g white reduced coenzyme Q10 powder (sample Sample 2) after filtering and drying in vacuum, the purity is 99.4%, the average powder particle size is 148 mm.
According to the method of Example 1, the proportion of reduced coenzyme Q10 of Sample 2 is determined by HPLC method, the weight ratio of reduced coenzyme Q10 to oxidized coenzyme Q10 in Sample 2 is 99.0/1.0.
According to the method of Example 1, X-ray diffraction spectrum of Samples 2 by the Cu-Ka ray X diffraction method is shown in Figure 2. In the diffraction spectrum, the diffraction Angle 2θ has strong peak at 3.0°, 4.6°, 20.1°, 22.8°, 27.4°, 30.3°, the diffraction Angle 2θ has a very strong absorption peak at 18.7°, 18.9°, and another diffraction Angle peak intensity is decreased obviously, the peak strength at peak 27.4° and 30.3° is less than 0.1 relative to peak 18.9°. A peak strength at 22.8°is as 100. A peak strength at 20.0° is less than 40.0. A peak strength at 18.9° is less than 90.0.
According to the method of Example 1, the melting point of Sample 2 is determined by thermogravimetric analyzer, Samples 2 by differential scanning thermal analyzer is scanned for melting point. The differential scanning map is shown in Figure 4, its melting point is 49.55 °C.

EXAMPLE 3 (Comparative example: crystallization)

30 g Sample 2 of Example 2 is dissolved in 20 times of sunflower oil, to dissolve under stirring at 60°C of temperature, and then cool to 5°C to crystallization, remove vegetable oil on the crystal surface with n-hexane after filtering, and dry under reduced pressure to obtain 25.6 g reduced coenzyme Q10 (Sample 3) with the purity of 98.9%.
According to the method of Example 1, the proportion of reduced coenzyme Q10 in Samples 3 is determined by HPLC method, the weight ratio of reduced coenzyme Q10 to oxidized coenzyme Q10 in Sample 2 is 99.1/0.9.

EXAMPLE 4: Experiment result of stability

Sample 1 and Sample 2 and Sample 3 obtained by Example 1, Example 2, Example 3 are respectively stored under shading or nitrogen for two months at 18°C. The retention rate of reduced coenzyme Q10 is respectively determined within 1 month and 2 months. The results are in Table 1.

Table 1

Sample	The retention rate of reduced coenzyme Q10 within 1 month	The retention rate of reduced coenzyme Q10 within 2 months
Sample 1	98.4%	95.5%
Sample
2	75.4%	66.3%
Sample 3	89.3%	85.4%

It can be seen from the result of Table 1, the stability of the reduced coenzyme Q10 powder obtained by the method is the best one. It still reaches 95.5% after 2 months. It is higher than the reduced coenzyme Q10 obtained by conventional method, with levels of 66.3% of Samples 2, 85.4% of Sample 3.

EXAMPLE 5: Experiment for calculating pharmacokinetic parameters of compounds and relative bioavailability thereof

Sample 1 and Sample 2 and Sample 3 obtained by Example 1, Example 2, Example 3 are used for beagle feeding experiment respectively, and the reduced coenzyme Q10 concentration in blood of feed beagle is determined, a basic pharmacokinetic parameters and relative bioavailability is calculated .

Experimental scheme is as follows:

4 beagles, half male and half female, 9-12 kg weight, provided by Shanghai Institute of Medicine Center for experimental animals, laboratory animals use license: SYXK (Shanghai), 2010-0049. A cross double cycle test is made. Gastric gavage is respectively for Sample 1, 2, 3, to fill stomach in a dose of 20 mg/kg, a delivery volume of 2 ml/kg. Samples with a suspension of soybean oil mixture for medicine (filling water 20 ml after feeding), normally feeding and drinking before testing, feeding feed containing meat on morning of the same day of feeding the medicine, to fill the stomach after 30 min. Two cycle tests are interval for a week.

Calculate the pharmacokinetic parameters of compounds by WinNonlin 5.3 software.

Peak-reaching time Tmax and peak-reaching concentration Cmax use measured values. Drug concentration area under time curve AUC_0-t value is calculated by the trapezoidal method, AUC_0-∞ is calculated by the formula AUC_0-∞= AUC_0-t + Ct/ke. Ct is a concentration measured by the last time point, ke is an eliminate rate constant, with half logarithmic mapping method, calculation by eliminating the concentration of the phase; Plasma elimination half-life t_1/2 = 0.693/ke. Relative bioavailability F = (AUC_0-t, Sample 2 or 3/AUC_0-t, Sample 1) × 100%. The main pharmacokinetic parameters after Beagle lavage for 20 mg/kg sample. Refer to Table 2:

Table 2

Sample		Tmax (h)	Cmax (ng/ml)	AUC_0-t (ng·h/ml)	AUC_0-∞ (ng·h/ml)	MRT (h)	t_1/2 (h)	F (%)
Sample 1	Average Standard deviation	7.5	303	3640	2865	10.9	6.11	/
	Average Standard deviation	3.0	103	1833	2150	2.5	2.67	/
Sample 2	Average Standard deviation	4.5	261	2359	2405	7.77	3.94	61.9
	Average Standard deviation	1.0	78	1181	1200	0.36	0.60	52.1
Sample 3	Average Standard deviation	6.3	287	2765	2658	8.35	4.76	74.7
	Average Standard deviation	1.9	83	1237	1890	1.81	1.76	49.5

It can be seen from Table 2 that the bioavailability of reduced coenzyme Q10 powder (samples 1) obtained by the method in beagle is significantly higher than that of the other two ways.
It can be seen from Examples 1 to 5 that in comparison with the crystallization method of the present invention and the Comparative Examples, the reduced coenzyme Q10 liquid of the present invention is sprayed in a sprayer, and particles after spraying in cold air has a lower crystallinity, and higher stability and bioavailability.

EXAMPLE 6

120mL acetone and 80mL deionized water are added to 60g oxidized coenzyme Q10, heated under stirring to 50°C, stirring for 1.0hr after adding 60g ascorbic acid sodium. 150mL n-hexane is added and placed after finishing the reaction, remove water of the lower layer, n-hexane of the upper layer is washed with 25% brine, and then to obtain a paste after recovering n-hexane, heat the paste up to 50°C.1g of natural vitamin E and 0.5g ascorbic acid as an antioxidant is added to a sprayer, and spray through the pressure sprayer, fog droplets is at 0°C nitrogen flow and shape immediately, finally obtain white reduced coenzyme Q10 powder 59.5 g. The purity is 96.3%, the average powder particle size is 210 mm.
According to the method of Example 1, the proportion of reduced coenzyme Q10 in the reduced coenzyme Q10 powder or crystals is determined by HPLC method, the proportion of reduced coenzyme Q10 / oxidized coenzyme Q10 is 99.4/0.6.
The reduced coenzyme Q10 powder is mixed with safflower seed oil, beeswax, and lecithin, to form a soft capsule, wherein the content of the reduced coenzyme Q10 is 50 mg per soft capsule for a dietary supplement.

EXAMPLE 7

1g vitamin A as antioxidant is added to 30g reduced coenzyme Q10 powder obtained by Example 6, and then mixed with 100g gelatin, 100g sugar, 35g dextrin, 25g glycerin solution to a pressure sprayer for spraying, droplets after spraying is in hot air of 190°C to dry and shape immediately, to obtain 284.5 g a white reduced coenzyme Q10 powder. The content of reduced coenzyme Q10 is 10.6%.
According to the method of Example 1, the proportion of reduced coenzyme Q10 in the reduced coenzyme Q10 powder or crystals are determined by HPLC method, the proportion of reduced coenzyme Q10 / oxidized coenzyme Q10 is 96.5/3.5.

EXAMPLE 8

150mL deionized water is added to 72g oxidized coenzyme Q10, heated under stirring to 50°C, to add 35g phosphorylation biological reductase for 4.0 hr and placed, to add 120mL n-hexane to remove water of the lower layer, and wash out of n-hexane of the upper layer with 25% brine, to obtain paste after recovering n-hexane, the paste is heated up to 50 °C, and then mixed with 0.5g BHT, 0.5g stearic acid, 3.0g oleic acid, and 1.0g linoleic acid in a pressure sprayer for spraying, droplets after spraying is in air without oxygen of 10°C to dry and shape immediately, to obtain 60.5 g white reduced coenzyme Q10 powder, with a purity 45.9%, and an average powder particle size 192 mm.

EXAMPLE 9

150mL ethanol are added to 55g oxidized coenzyme Q10, heated under stirring to 50°C, add 50g carboxylic acid sodium disulfide under stirring for reaction 1.0 hr and placed after finishing the reaction, and add 120mL n-hexane and 100mL deionized water, remove water of the lower layer, and wash out of n-hexane of the upper layer with 25% brine, to obtain paste after recovering n-hexane, the paste is heated up to 50°C, , and then mixed with 0.8g antioxidant butylated hydroxy toluene (BHT) and 0.8g vitamin A, 3.0g polyglycerol fatty acid ester in a pressure sprayer for spraying, droplets after spraying is in nitrogen air of 30°C to dry and shape immediately, to obtain white reduced coenzyme Q10 powder 53.5g, with a purity of 90.9%, an average powder particle size of 203 mm.

EXAMPLE 10

40 g reduced coenzyme Q10 powder of Example 9 is mixed with 25g sodium caseinate, 18g modified starch, 37g cyclodextrin, 16g gum Arabic, 10g soybean protein solution in a centrifugal sprayer for spraying, droplets after spraying is in hot air of 180°C to dry and shape immediately, to obtain white reduced coenzyme Q10 powder 142.5 g. The content of reduced coenzyme Q10 is 20.8%.

Claims

A method for preparing a reduced coenzyme Q10 powder, wherein the method comprising the steps as follows:
(1) adding an oxidized coenzyme Q10 into an organic solvent, heating to 50 °C∼ 60°C of temperature, and adding a reductant for reaction; wherein the reductant is selected from one or more of hyposulphurous acid or salt thereof, ascorbic acid or salt thereof, carbodithioic acid or salt thereof, or reductase; the organic solvent is ketones, or hydrophobic alkanes; and

(2) removing the organic solvent after finishing the reaction to obtain a molten and oily reduced coenzyme Q10 liquid; and then heating the molten and oily reduced coenzyme Q10 liquid to 50°Cof temperature, spraying by a centrifugal sprayer, to form particles in cold air after spraying, to obtain a white reduced coenzyme Q10 powder.
A method according to claim 1, wherein the hyposuphurous acid or salt thereof is thiosulfuric acid or sodium thiosulfate; the ascorbic acid or salt thereof is ascorbic acid or sodium ascorbate; the dithiosulfuric acid or salt thereof is dithiosulfuric acid or sodium dithiosulfate; the reductase is phosphorylation biological reductase; the ketone is acetone; the hydrophobic paraffin is n-hexane.
A method according to claim 1, wherein the temperature of the cold air is not higher than 30°C.
A method according to claim 1, wherein the temperature of the cold air is not higher than 10°C.
A method according to claim 1, wherein the cold air is conventional air, air without oxygen or nitrogen.
A method according to claim 1, wherein spraying is performed by using a centrifugal sprayer or pressure sprayer when spraying.
A method according to claim 1, further comprising adding antioxidant, stabilizer, absorption enhancer and/or excipient as adjuvants to the reduced coenzyme Q10 liquid before spraying, to obtain the reduced coenzyme Q10 powder with adjuvants; or re-melting the reduced coenzyme Q10 powder or the reduced coenzyme Q10 powder with the adjuvants, and then mixing it with antioxidant, stabilizer, absorption enhancer and/or excipient as adjuvants, to obtain the reduced coenzyme Q10 powder by a spraying drying method.
A method according to claim 7, wherein the antioxidant is selected from one or more of vitamin E, butyl hydroxy toluene, ascorbic acid and vitamin A; the stabilizer is selected from one or more of gelatin, casein, sodium caseinate, soybean protein, modified starch, cyclodextrin and gum Arabic; the absorption enhancer is selected from one or more of polyglycerol fatty acid ester, glycerin, stearic acid, oleic acid and linoleic acid; the excipient is sugar and/or dextrin.
A method according to claim 7, comprising adding antioxidants and/or stabilizers, and/or excipients, and/or absorption enhancer to the reduced coenzyme Q10 liquid, and then spraying in a sprayer, drying and styling the sprayed drops at 190°C of temperature in hot air after spraying, to obtain the reduced coenzyme Q10 powder.
A method according to claim 1, wherein the dosage form of the reduced coenzyme Q10 powder is tablets or capsules, for dietary supplement.